Asymmetric Addition of Diethylzinc to Aldehydes Catalyzed by Metal Complexes with Chitosan and D -(+)-Glucosamine Derivatives as a Ligand

THE SCIENCE AND ENGINEERING REVIEW OF DOSHISHA UNIVERSITY, VOL. 52, NO.2July2011

Asymmetric Addition of Diethylzinc to Aldehydes Catalyzed by Metal Complexes with Chitosan and D -(+)-Glucosamine Derivatives as a Ligand

Tetsuo O

HTA

,* Noriteru M

AEDA

,** Ryo K

UJIME

,** Yohei O

E

,* Takayuki Y

AMASHITA

,** and Isao F

URUKAWA

**

(Received March 23, 2011)

Chitin is an ubiquitous natural biopolymer consisted of D-glucosamine with E-(1,4) bonds but hardly used for chemical transformation because of its extremely low solubility. On the other hand, chitosan is easily obtained from chitin by deacetylation and soluble in acidic media. It is also optically active and expected to be used as a chiral source, if it could be soluble in organic solvent. Chitosan and its monomer, D-(+)-glucosamine, were modified in order to become soluble in organic solvent and examined as a chiral ligand for asymmetric addition of diethylzinc to aldehydes. First, chemically modified chitosans were synthesized from chitosan, and used as a ligand. Although the reaction of benzaldehyde with Et2Zn in the presence of chitin and chitosan gave the racemic 1-phenyl-1-propanol, N-phthaloyl-6-O-tritylchitosan as a ligand accelerated the reaction to produce (R)-1-phenyl-1-propanol with up to 61% ee. Next, D-(+)-glucosamine derivatives were synthesized and used as a ligand. Benzyl-2-acetylamino-4,6-O- anisylidene-2-deoxy-D-D-glucopyranoside and Ti complex accelerated the reaction and was found to be the most efficient catalyst for the asymmetric addition to the various aldehydes with diethylzinc, giving the (R)-1-phenyl-1-propanol in high yield with high enantiomeric excess up to 94%.

Key Words : Chitosan, Glucosamine, Asymmetric Addition, Diethylzinc

ࠠ࡯ࡢ࡯࠼㧦ࠠ࠻ࠨࡦ㧘ࠣ࡞ࠦࠨࡒࡦ㧘ਇᢧઃട෻ᔕ㧘ࠫࠛ࠴࡞੝㋦

ࠠ࠻ࠨࡦ㧘 D -(+)- ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ࠍ㈩૏ሶߣߔࠆ㊄ዻ㍲૕ሽ࿷ਅߢߩ

ࠫࠛ࠴࡞੝㋦ߩ⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩ⸅ᇦ⊛ਇᢧઃട෻ᔕ

ᄥ↰ື↵㧘೨↰ᙗノ㧘ਭᰴ☨੫㧘ᄢᳯᵗᐔ㧘ጊਅ㓉ਯ㧘ฎᎹഞ

㧚߹߃߇߈

ࠠ࠴ࡦߪਅ╬േ‛㧘․ߦ▵⿷േ‛ߦᄙߊ฽߹ࠇ ߡ߅ࠅ㧘ᐕ㑆ߦ↢วᚑߐࠇࠆ㊂ߪ⤘ᄢߢ㧘ᢙචం

࠻ࡦߣផቯߐࠇߡ޿ࠆ㧚ߎߩࠃ߁ߦ⥄ὼ⇇ߦ⼾ን ߦሽ࿷ߒ㧘ߒ߆߽ኈᤃߦᓧࠄࠇࠆߦ߽߆߆ࠊࠄߕ㧘

ࠠ࠴ࡦߪ࠮࡞ࡠ࡯ࠬߦᲧߴࠆߣ೑↪߇࿎㔍ߢ޽ࠆ ߚ߼㧘߶ߣࠎߤ߇ᑄ᫈ߐࠇߡ޿ࠆ㧚߹ߚࠠ࠴ࡦࠍ

⣕ࠕ࠮࠴࡞ൻߒߚࠠ࠻ࠨࡦ߽ D

-

ࠣ࡞ࠦࠨࡒࡦ᭴ㅧ ࠍၮ⋚ߣߔࠆࡃࠗࠝࡐ࡝ࡑ࡯ߢ㧘╙৻⚖ࠕࡒࡁၮ ߣ᳓㉄ၮࠍ᦭ߔࠆߎߣ߆ࠄ᭽ޘߥᯏ⢻ᕈ㜞ಽሶߣ

*Department of Biomedical Information, Doshisha University, Kyotanabe, Kyoto Telephone: +81-774-65-6548, FAX: +81-774-65-6789, E-mail: [email protected]

ߒߡߩ೑↪߇น⢻ߢ޽ࠅ㧘ක≮ಽ㊁㧘㘩ຠಽ㊁㧘

⚛᧚ಽ㊁ߥߤߩ⎇ⓥ߇ႎ๔ߐࠇߡ޿ࠆ¹⁾㧚

৻ᣇ㧘⥄ὼ⇇ߦߪਇᢧ὇⚛ේሶࠍ߽ߟ᭽ޘߥᄤ ὼ‛߇ሽ࿷ߒ㧘↢๮ᵴേߩᩮᐙࠍᜂߞߡ޿ࠆ㧚߹

ߚ㧘ක⮎㧘ㄘ⮎㧘㚅ᢱ㧘↢ಽ⸃ᕈࡊ࡜ࠬ࠴࠶ࠢ㧘 ᶧ᥏ߥߤᯏ⢻ᕈ᧚ᢱߦ߅޿ߡ߽ਇᢧ὇⚛ේሶࠍ᦭

ߔࠆ‛⾰ߩ㊀ⷐᕈ߇ᵈ⋡ߐࠇߡ޿ࠆ㧚ਇᢧวᚑ෻

ᔕߪ㧘ࠕࠠ࡜࡞߹ߚߪࡊࡠࠠ࡜࡞ߥൻว‛߆ࠄਇ ᢧ὇⚛ේሶࠍ᭴▽ߔࠆ෻ᔕߢ޽ࠆ߇㧘ਇᢧḮࠍൻ ቇ㊂⊛ߦ↪޿ࠆᣇᴺߪ㜞ଔߥਇᢧḮࠍᄙ㊂ߦ↪޿

ࠆߚ߼Ꮏᬺࡊࡠ࠮ࠬߣߒߡߪታ↪⊛ߢߪߥ޿㧚ߘ ߎߢ㧘቟ଔߦ㧘߆ߟ㧘ዋ㊂ߩਇᢧḮ߆ࠄᄙߊߩశ ቇᵴᕈ૕ࠍᓧࠄࠇࠆ⸅ᇦ෻ᔕߩ㐿⊒߇ㅴ߼ࠄࠇߡ ߈ߚ²⁾㧚

ᓥ᧪㧘ࠕ࡞࠺ࡅ࠼߅ࠃ߮ࠤ࠻ࡦ㘃߳ߩ᦭ᯏ㊄ዻ ൻว‛ߩઃടߦࠃࠆࠕ࡞ࠦ࡯࡞㘃ߩวᚑߪ㧘෻ᔕ ᵴᕈߩ㜞޿᦭ᯏ࡝࠴࠙ࡓ߅ࠃ߮

Grignard

⹜⮎߇↪

޿ࠄࠇߡ߈ߚ㧚৻ᣇ㧘ߎࠇ߹ߢ෻ᔕਇᵴᕈߣߐࠇ ߡ߈ߚࠫࠛ࠴࡞੝㋦߇ࠕࡒࡁࠕ࡞ࠦ࡯࡞ߩࠃ߁ߥ

⸅ᇦሽ࿷ਅߦ߅޿ߡࠕ࡞࠺ࡅ࠼ߦઃടߔࠆߎߣ߇

⷗಴ߐࠇ㧘శቇᵴᕈഥ⸅ᇦߣߒߡశቇᵴᕈ ȕ㧙ࠕ ࡒࡁࠕ࡞ࠦ࡯࡞ߥߤࠍ↪޿ߚਇᢧวᚑ෻ᔕ߇ᄙߊ ႎ๔ߐࠇߡ߈ߚ

(Scheme 1)

^3-6)㧚

O

H + Et₂Zn

ligand OH

MeN SH

Ph 82 %ee

Ph Me

HO NBu₂ 93 %ee CH₂Cl₂

Scheme 1. Asymmetric addition of diethylzinc to

benzaldehyde.

ߒ߆ߒ㧘↪޿ࠄࠇࠆశቇᵴᕈࠕࡒࡁࠕ࡞ࠦ࡯࡞

ߥߤశቇᵴᕈൻว‛ߪ㜞ଔߢ޽ࠅ㧘߹ߚ౉ᚻ߇ኈ ᤃߢߥ޿ߎߣ߇ᄙ޿^7-9)㧚

ᧄ⎇ⓥߢߪ㧘ࠠ࠻ࠨࡦ߇శቇᵴᕈ㜞ಽሶߢ޽ࠅ㧘

㊄ዻߣࠠ࡟࡯࠻᭴ㅧ ¹⁰⁾ ࠍᒻᚑߢ߈ࠆߎߣ߆ࠄ㧘ࠠ

࠻ࠨࡦ⺃ዉ૕ࠍ↪޿ࠆࡌࡦ࠭ࠕ࡞࠺ࡅ࠼߳ߩࠫࠛ

࠴࡞੝㋦ߩਇᢧઃട෻ᔕߦߟ޿ߡᬌ⸛ߒߚ㧚ߐࠄ ߦ㧘ࡃࠗࠝࡐ࡝ࡑ࡯

(

ࠠ࠻ࠨࡦ

)

ߩ᭴ᚑන૏ߢ޽ࠆ ࠕࡒࡁ♧ߩ D

-(+)-

ࠣ࡞ࠦࠨࡒࡦߩ⺃ዉ૕ࠍวᚑߒ㧘

⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕߦኻߔࠆ⸅

ᇦലᨐߦߟ޿ߡᬌ⸛ߒߚ㧚

㧚ታ㛎ᣇᴺ ⹜⮎ߩ⺞ᢛ

DMF

ߪ

bp. 78-79 °C / 6 Torr

ߩ⇐ಽࠍ㧘

DMSO

ߪ

bp. 85-87 °C / 25 Torr

ߩ⇐ಽࠍ૶↪ߒߚ㧚߶߆ߩṁ ᇦߪᏱᴺߦࠃࠅ⣕᳓ߒߚᓟ㧘⫳⇐ߒߚ߽ߩࠍ૶↪

ߒߚ㧚਄⸥ߩߔߴߡߩṁᇦߪ㧘⫳⇐ᓟࠕ࡞ࠧࡦࠟ

ࠬߢ

10

ಽ㑆⣕᳇ߒ㧘ࡕ࡟ࠠࡘ࡜࡯ࠪ࡯ࡉࠬ

4A

ࠍ ട߃ߡࠕ࡞ࠧࡦ㔓࿐᳇ਅߢ଻ሽߒߚ㧚ࡇ࡝ࠫࡦߪ

࠽ࠞ࡜ࠗ࠹ࠬࠢ․⚖⹜⮎ࠍᏱᴺߦࠃࠅ⫳⇐♖⵾ߒ ߚ߽ߩࠍ૶↪ߒߚ㧚ฦ⒳⹜⮎ߪ㧘Ꮢ⽼ຠࠍߘߩ߹

߹૶↪ߒߚ㧚ࠪ࡝ࠞࠥ࡞ߪ㧘ࠞ࡜ࡓࠢࡠࡑ࠻ࠣ࡜

ࡈ↪࠽ࠞ࡜ࠗ࠹ࠬࠢࠪ࡝ࠞࠥ࡞

60 (70-140 mesh)

ࠍ૶↪ߒߚ㧚

᷹ቯ㧘ಽᨆᯏེ

1

H NMR

᷹ቯߪᣣᧄ㔚ሶ⵾ JNM-Į400 (400 MHz, G / ppm)㧘

IR

᷹ቯ

(KBr,Q/ cm

^-1

)

ߪፉᵤ⵾૞ᚲ⵾

IR-408

߽ߒߊߪࡈ࡯࡝ࠛᄌ឵⿒ᄖಽశⵝ⟎

(FT-

IR) NICOLET 800

ဳ㧘ࠟࠬࠢࡠࡑ࠻ࠣ࡜ࡈࠖ࡯

(GC)

ߪፉᵤ⵾૞ᚲ⵾

GC-14B (Column: SE-30 on Chromosorb W (AW-DMCS 80-100 mesh, 4 mmI x 2 m)㧘ࠟࠬࠢࡠࡑ࠻ࠣ࡜ࡈࠖ࡯⾰㊂ಽᨆ⸘ (GC-MS)

ߪፉᵤ⵾૞ᚲ⵾

QP-2000A

㧘㜞ㅦᶧ૕ࠢࡠࡑ࠻ࠣ

࡜ ࡈ ࠖ ࡯

(HPLC)

ߪ ፉ ᵤ ⵾ ૞ ᚲ ⵾

LC-6A

(Column: DAICEL CHIRALCEL OJ-R, 4.6 mmI x 15

cm, MeOH / H

2

O = 50 / 50, 0.30 mL / min., Detector

SPD-10A, 220 nm)

߽ߒߊߪ

HITACHI

⵾

L-7100

(Column: DAICEL CHIRALCEL OD-H, 4.6 mmIx 25

cm, n-Hex / i-PrOH = 99 / 1, 0.50 mL / min., Detector

L-7400, 254 nm)

߽ ߒ ߊ ߪ ፉ ᵤ ⵾ ૞ ᚲ ⵾

LC-6A

(Column: DAICEL CHIRALCEL OB, 4.6 mmIx 25

cm,

n-Hex / i-PrOH = 99 / 1, 0.50 mL/min., Detector

SPD-6A, 254 nm)

㧘ᣓశ⸘ߪၳ႐⵾૞ᚲ⵾

SEPA-

115

200

ࠍ↪޿ߡⴕߞߚ㧚㆙ᔃಽ㔌ᯏߪᣣ┙⵾૞ᚲ⵾

CT5DL

ࠍ 㧘 ⭯ ጀ ࠢ ࡠ ࡑ ࠻ ࠣ ࡜ ࡈ ࠖ ࡯

(TLC)

ߪ

M.NAGEL

␠⵾ࠪ࡝ࠞࠥ࡞

60

ࡊ࡟࡯࠻

F254

ࠍ↪

޿ߚ㧚

⒳ޘߩࠠ࠻ࠨࡦ⺃ዉ૕ߩวᚑ

ࠠ࠴ࡦ

(1a)

㧘ࠠ࠻ࠨࡦ

(1b)

ࠠ࠴ࡦߪ࠽ࠞ࡜ࠗ࠹ࠬࠢ⵾․⚖⹜⮎

(from Crab

Shells)

ࠍ૶↪ߒߚ㧚߹ߚࠠ࠻ࠨࡦߪ๺శ⚐⮎⵾৻

⚖⹜⮎⣕ࠕ࠮࠴࡞ൻᐲ 89.3% ߩ߽ߩࠍ૶↪ߒߚ㧚

6-O-

࠻࡝࠴࡞ࠠ࠻ࠨࡦ

(1c)

¹¹⁾

IR (KBr): 3400, 2900, 700.

¹

H NMR (DMSO-d

6

): 7.2- 7.6 (Ar-H).

N-

ࡌࡦࠫ࡞ࠠ࠻ࠨࡦ

(1d)

ਃⷺࡈ࡜ࠬࠦ

(50 mL)

ߦࠠ࠻ࠨࡦ

(0.20 g, 1.24 mmol)㧘⥇ൻࡌࡦࠫ࡞ (0.34 g, 1.99 mmol)㧘᳓ (10 mL)

ࠍ౉ࠇ㧘

24

ᤨ㑆ടᾲㆶᵹߒߚ㧚෻ᔕᓟᷫ࿶ਅ ߢỚ❗ߒ㧘ࠕ࠮࠻ࡦߦౣᴉᲚߐߖߚᓟ㧘ࠕ࠮࠻ࡦ ߢᵞᵺߒ㧘ᷫ࿶ੇ῎ߐߖߡ☳ᧃ⁁ߩ↢ᚑ‛

0.27 g (86.1%)

ࠍᓧߚ㧚

IR (KBr): 3390, 1615, 650.

¹

H NMR (DMSO-d

6

): 7.2-7.6 (Ar-H), 8.3(-N

⁺

H

2

-).

N-ࡌࡦࠫ࡞-6-O-࠻࡝࠴࡞ࠠ࠻ࠨࡦ (1e)

ਃⷺࡈ࡜ࠬࠦ

(50 mL)

ߦ1c (1.00 g, 2.48 mmol)㧘 ࡌࡦ࠭ࠕ࡞࠺ࡅ࠼

(1.32 g, 12.4 mmol)

㧘

DMF (20 mL)

ࠍ౉ࠇ㧘ቶ᷷ߢ

24

ᤨ㑆ᡬᜈߒߚ㧚ࠫࠛ࠴࡞

ࠛ࡯࠹࡞ਛߦᵈ߉㧘ౣᴉᲚߐߖߚᓟ㧘ࠫࠛ࠴࡞ࠛ

࡯࠹࡞ߢᵞᵺߒ㧘ᷫ࿶ੇ῎ߐߖߚ㧚

IR (KBr): 3400, 1600, 730, 680, 630.

ᰴ޿ߢ↢ᚑ‛ࠍ㧘ਃⷺࡈ࡜ࠬࠦ

(100 mL)

ߦ౉

ࠇ㧘

DMF (50 mL)

ࠍട߃ᡬᜈߒṁ⸃ߐߖߚᓟ㧘᳓

⚛ൻࡎ࠙⚛࠽࠻࡝࠙ࡓ

(0.18 g)

ࠍട߃㧘ቶ᷷ߢ

24

ᤨ㑆ᡬᜈߒߚ㧚෻ᔕᶧࠍࠫࠛ࠴࡞ࠛ࡯࠹࡞ਛߦᵈ ߉ౣᴉᲚߐߖߚᓟ㧘ࠫࠛ࠴࡞ࠛ࡯࠹࡞ߢᵞᵺߒ㧘

ᷫ࿶ੇ῎ߐߖߡ☳ᧃ⁁ߩ1e 1.00 g (81.7%) ࠍᓧߚ㧚

IR (KBr): 3400, 730, 680, 630.

N-ࡈ࠲ࡠࠗ࡞ࠠ࠻ࠨࡦ

(2a)

¹¹⁾

IR (KBr): 3400, 2900, 1700, 700.

¹

H NMR (DMSO-d

6

):

7.4-7.8(broad, Ar-H).

¹³

C NMR (DMSO-d

6

): 160.8- 168.1, 123.3-134.6, 97.2, 78.9, 74.6, 71.7, 68.6, 59.5.

N-

ࡈ࠲ࡠࠗ࡞

-3,6-O-

ࠫࠕ࠮࠴࡞ࠠ࠻ࠨࡦ

(2b)

¹¹⁾

IR (KBr): 3400, 2925, 1750, 1320,720.

¹

H NMR (CDCl

3

): 2.6(broad, -COCH

3

).

¹³

C NMR (CDCl

3

): 168- 169, 123.7-134, 96.0, 70.0-75.5, 55.1, 20.1-20.5.

N-ࡈ࠲ࡠࠗ࡞

-6-O-

࠻࡝࠴࡞ࠠ࠻ࠨࡦ

(2c)

¹¹⁾

IR (KBr): 3400, 2900, 1700, 700.

¹

H NMR (DMSO-d

6

):

7.0-7.8 (Ar-H).

¹³

C NMR (DMSO-d

6

): 167.3, 143.2- 147.7, 123.2-134.5, 50.0-100.0.

N-ࡈ࠲ࡠࠗ࡞

-6-O-

ࡈࠚ࠾࡞ࠞ࡞ࡃࡕࠗ࡞ࠠ࠻ࠨ ࡦ (2d)

ਃญ෻ᔕኈེ

(50 mL)

ࠍࠕ࡞ࠧࡦ㔓࿐᳇ਅߦߒ㧘 ߎࠇߦ 2a (5.00 g, 17.2 mmol), ࠗ࠰ࠪࠕࡦ㉄ࡈࠚ࠾

࡞

(4.00 g, 34.0 mmol)

㧘ࡇ࡝ࠫࡦ

(10 mL)

ࠍ㗅ᰴ

ട߃㧘

80

°Cߢ

24

ᤨ㑆ടᾲㆶᵹߒߚ㧚෻ᔕᓟࠫࠛ

࠴࡞ࠛ࡯࠹࡞ਛߦᵈ߉㧘ౣᴉᲚߐߖߚᓟ㧘ᴉốࠍ

ࠛ࠲ࡁ࡯࡞ߢᵞᵺߒ㧘ᷫ࿶ੇ῎ߐߖߡ☳ᧃ⁁ߩ↢

ᚑ‛

5.79 g (63.6%)

ࠍᓧߚ㧚

IR (KBr): 3300, 1640, 1590, 1716, 1450, 750, 721, 697.

¹

H NMR (CDCl

3

):

6.9-7.6 (broad, Ar-H),

¹³

C NMR (CDCl

3

): 167.9, 152.7- 153.3, 123.5-134.1, 118.3-120.2, 50.0-100.0.

N-ࡈ࠲ࡠࠗ࡞

-6-O-

ࠫࡔ࠴࡞ࠞ࡞ࡃࡕࠗ࡞ࠠ࠻ࠨ ࡦ (2e)

ਃญ෻ᔕኈེ

(100 mL)

ࠍࠕ࡞ࠧࡦ㔓࿐᳇ਅߦߒ㧘 2a (2.00 g, 6.87 mmol)㧘ࡇ࡝ࠫࡦ

(30 mL)

ࠍട߃㧘 ဋ৻ߦߥࠆ߹ߢߒ߫ࠄߊᡬᜈߒߚᓟ㧘ࠫࡔ࠴࡞ࠞ

࡞ࡃࡕࠗ࡞ࠢࡠ࡝࠼

(2.50 mL, 27.2 mmol)

ࠍട߃㧘

80

°Cߢ

24

ᤨ㑆ടᾲㆶᵹߒߚ㧚෻ᔕ⚳ੌᓟ㧘ࠛ࠲

ࡁ࡯࡞ਛߦᵈ߉㧘ౣᴉᲚߐߖߚᓟ㧘ࠛ࠲ࡁ࡯࡞㧘

ࠫࠛ࠴࡞ࠛ࡯࠹࡞ߢᵞᵺߒ㧘ᷫ࿶ੇ῎ߐߖߡ☳ᧃ

⁁ߩ↢ᚑ‛

1.65 g (55.4%)

ࠍᓧߚ㧚

IR (KBr): 3400, 2900, 1700, 1610, 720.

¹

H NMR (DMSO-d

6

):

2.5(N(CH

3

)

2

), 7.0-8.0(broad, Ar-H).

¹³

C NMR (DMSO- d

6

): 164.1-169.2, 123.4-138.4, 96.9, 71.5, 68.1, 56.7- 56.9, 33.9.

ࠠ࠴ࡦ㧘ࠠ࠻ࠨࡦ߅ࠃ߮ࠠ࠻ࠨࡦ⺃ዉ૕ࠍ㈩

૏ሶߣߔࠆࠫࠛ࠴࡞੝㋦ߦࠃࠆ⧐㚅ᣖࠕ࡞࠺ࡅ࠼

㘃߳ߩਇᢧઃട෻ᔕ

ࡈ࡟࡯ࡓ࠼࡜ࠗߒߚࠪࡘ࡟ࡦࠢ࠴ࡘ࡯ࡉߦࠠ࠻

キトサン，D-(+)-グルコサミン誘導体を配位子とする金属錯体存在下でのジエチル亜鉛の芳香族アルデヒド類への触媒的不斉付加反応

ࠨࡦ⺃ዉ૕

(0.5 mmol / 1 unit)

ࠍ౉ࠇ㧘⌀ⓨ࡜ࠗࡦ ߢචಽߦੇ῎ߒߚߩߜ㧘ࠕ࡞ࠧࡦࠟࠬ㔓࿐᳇ਅࠫ

ࠢࡠࡠࡔ࠲ࡦ

(10 mL)

ࠍ౉ࠇ㧘

0

°Cߢ㧘ࠫࠛ࠴࡞

੝㋦

1.0 M

ࡋࠠࠨࡦṁᶧ (1.0 mmol, 1.0 mL) ࠍṢ ਅ ߒ 㧘 㧝 ᤨ 㑆 ᡬ ᜈ ߒ ߚ ᓟ 㧘 ࡌ ࡦ ࠭ ࠕ ࡞ ࠺ ࡅ ࠼

(0.106 g, 1 mmol)

ࠍട߃㧘ߎࠇߦౣᐲࠫࠛ࠴࡞੝

㋦

(2.4 mmol, 2.4 mL)

ࠍṢਅߒ㧘

24

ᤨ㑆ᡬᜈߒߚ㧚 ߎߩ෻ᔕᷙวṁᶧߦ

1M

Ⴎ㉄ࠍട߃෻ᔕࠍ⚳ੌߐ ߖߚᓟ㧘ࠫࠛ࠴࡞ࠛ࡯࠹࡞

(30 mL)

ࠍട߃ࠈ೎ߒ ߚ㧚ࠈᶧߦ

1M

Ⴎ㉄ࠍട߃ᵞᵺᓟ㧘ࠫࠛ࠴࡞ࠛ࡯

࠹࡞ጀࠍ⎫㉄ࡑࠣࡀࠪ࠙ࡓߢੇ῎㧘ᷫ࿶Ớ❗ߒ㧘 ᓧࠄࠇߚ↢ᚑ‛ࠍ

GC

㧔ౝㇱᮡḰ㧦ࠫࡈࠚ࠾࡞㧕㧘

HPLC

㧘ᣓశశᐲ⸘ߢಽᨆߒߚ㧚

D

-(+)-

ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ߩวᚑ

2-ࠕ࠮࠻ࠕࡒࡁ-2-࠺ࠝࠠࠪ-D-D

-ࠣ࡞ࠦ࡯ࠬ (3) mp. 203-205 °C (decomp), [D]

²⁰_D

+45.1° (c = 1.0, H

₂

O) (Lit.

¹²⁾

mp. 204 °C, [D]

²⁰D

+45° (c = 1.0, H

2

O)).

ࡌࡦࠫ࡞

-2-

ࠕ࠮࠻ࠕࡒࡁ

-2-

࠺ࠝࠠࠪ

-D-D-

ࠣ࡞

ࠦࡇ࡜ࡁࠪ࠼

(4)

mp. 184-189 °C, [D]

²⁵_D

+165.1° (c = 1.0, DMF) (Lit.

¹²⁾

mp. 183-184 °C, [D]

²⁰D

+165.1° (c = 1.0, H

2

O)).

ࡌࡦࠫ࡞

-2-

ࠕ࠮࠻ࠕࡒࡁ

-6-O-

࠻࡝࠴࡞

-2-

࠺ࠝ

ࠠࠪ

-D-

D

-

ࠣ࡞ࠦࡇ࡜ࡁࠪ࠼

(5)

ߩวᚑ

ࡌࡦࠫ࡞

-2-

ࠕ࠮࠻ࠕࡒࡁ

-2-

࠺ࠝࠠࠪ

-

ǩ

-

㧰

-

ࠣ࡞ࠦ

ࡇ࡜ࡁࠪ࠼

(4) (16 mmol, 5.0 g)

ࠍࡇ࡝ࠫࡦ

(5 mL)

ߦട߃㧘Ⴎൻ࠻࡝࠴࡞

(20.0 mmol, 5.56 g)

ࠍട߃ ߡ

80

°C ߢᡬᜈߒߚ㧚෻ᔕ⚳ੌᓟ㧘಄᳓ߢᴉᲚߐ ߖ㧘ࠛ࠲ࡁ࡯࡞ࠃࠅౣ⚿᥏ߒߚ㧚෼㊂

6.38 g (74%), mp. 120-124 °C, [D]

²⁵D

+50° (c = 1.0, DMF). IR (KBr):

3300, 3050, 2900, 1650, 1590, 1490, 1440, 1370, 1310, 1210, 900, 850, 750, 700.

¹

H NMR (d

⁶

-DMSO): 7.22- 7.48 (m, 20H, arom-H), 5.85 (d, J = 8.0 Hz, 1H, NH), 4.92 (d, J = 4.0 Hz, 1H, 1-H), 4.80 (d, 1H, J = 12.4 Hz, Ph-CH-), 4.50 (d, 1H, J = 12.4 Hz, Ph-CH-), 4.12 (m, 1H, 4-H), 3.74-3.79 (m, 1H, 3-H), 3.61-3.71 (m, 1H, 5- H), 3.56-3.60 (m, 1H, 2-H), 3.33-3.42 (m, 2H, 6-H

2

), 1.61 (s, 3H, -COCH

3

).

ࡌࡦࠫ࡞

-2-

ࠕ࠮࠻ࠕࡒࡁ

-4,6-O-

ࠕ࠾ࠪ࡝࠺ࡦ

-

2-

࠺ࠝࠠࠪ

-D-

D

-

ࠣ࡞ࠦࡇ࡜ࡁࠪ࠼

(6)

ߩวᚑ

DMF (10 mL)

ߦ਄⸥ߢᓧࠄࠇߚ 4 (5.30 mmol, 1.66

g)

ࠍട߃ߡ㧘

80

°C ߢᡬᜈߒߚ㧚ဋ৻ߥ⁁ᘒߦߥ ߞߚᓟ㧘p-࠻࡞ࠛࡦࠬ࡞ࡎࡦ㉄ࡇ࡝ࠫࡦႮ (0.04

mmol, 10 mg)

ࠍട߃ߚ㧚ᰴ޿ߢp-ࠕ࠾ࠬࠕ࡞࠺ࡅ

࠼ࠫࡔ࠴࡞ࠕ࠮࠲࡯࡞

(6.2 mmol, 1.13 g)

ߩ

DMF

(10 mL)

ṁᶧࠍṢਅߒ㧘

24

ᤨ㑆ᡬᜈߒߚ㧚෻ᔕ⚳

ੌᓟ㧘Ớ❗ߒ㧘

NaHCO

3

(1 g, 50 mL)

᳓ṁᶧߦട߃㧘 ᨆ಴ߒߚᴉᲚ‛ࠍࠈ೎ߒ㧘᳓ߢචಽᵞᵺᓟ㧘ዋ㊂ ߩࠛ࠲ࡁ࡯࡞ߢ㧘ߐࠄߦࠫࠛ࠴࡞ࠛ࡯࠹࡞ߢᵞᵺ ߒߚᓟ㧘ࠛ࠲ࡁ࡯࡞ࠃࠅౣ⚿᥏ߒߚ㧚↢ᚑ‛ߪ

1

H-NMR

ߦࠃࠅหቯߒߚ㧚෼㊂

2.04 g (90%), mp.

269

°C, [D]²⁵_D

+102° (c = 1.0, DMF). IR(KBr): 3400, 3250, 3050, 2950, 2850, 1620, 1550, 1510, 1370, 1300, 1250, 1170, 960, 910, 830, 790, 730, 690, 670.

¹

H NMR (d

⁶

-DMSO): 8.00 (d, J = 8.0 Hz, 1H, NH), 6.89-7.39 (m, 9H, arom-H), 5.55 (s, 1H, An-CH-), 5.18 (s, 1H, 3-OH), 4.78 (d, J = 4.0 Hz, 1H, 1-H), 4.69 (d, J = 12.8 Hz, 1H, Ph-CH-), 4.48 (d, J = 12.4 Hz, 1H, Ph-CH-), 4.12 (dd,

J1

= 10.0 Hz, J

2

= 9.0 Hz, 1H, 4-H), 3.80-3.85 (m, 1H, 3-H), 3.74 (s, 3H, CH

3

O-), 3.42-3.54 (m, 3H, 2-H, 6- H

2

), 3.01-3.16 (m, 1H, 5-H), 1.84 (s, 3H, -COCH

3

).

ࡌࡦࠫ࡞

-2-

ࠕ࠮࠻ࠕࡒࡁ

-4,6-O-

ࡌࡦࠫ࡝࠺ࡦ

- 2-

࠺ࠝࠠࠪ

-D-

D

-

ࠣ࡞ࠦࡇ࡜ࡁࠪ࠼

(7)

mp. 259-260 °C, [D]

²⁵_D

+88° (c = 1.0, DMF) (Lit.

¹²⁾

mp.

262 °C, [D]

²³D

+114° (c = 1.1, pyridine)).

ࡔ࠴࡞

-4,6-O-

ࠕ࠾ࠪ࡝࠺ࡦ

-

D

-

ࠣ࡞ࠦࡇ࡜ࡁࠪ

࠼ (8)

FAB-MS: m/z 313, mp. 199-202 °C (Lit.

¹³⁾

mp. 183- 186 °C, [D]

²⁵D

+99°(c = 1.0, CHCl

3

)).

ࡌࡦࠫ࡞

-D-

D

-

ࠣ࡞ࠦࠪ࠼ߩวᚑ

ࡌࡦࠫ࡞ࠕ࡞ࠦ࡯࡞

(95 mL)

ߦႮൻࠕ࠮࠴࡞

(1 mL)

㧘D-D

-

ࠣ࡞ࠦ࡯ࠬ

(106 mmol, 23.5 g)

ࠍട߃㧘

30

ಽ㑆ടᾲㆶᵹߒߚ㧚෻ᔕ⚳ੌᓟ㧘ዋ㊂ߩή᳓ࠫ

ࠛ࠴࡞ࠛ࡯࠹࡞ࠍട߃㧘⦟ߊ߆߈ᷙߗߚᓟ㧘᦭ᯏ ጀࠍᝥߡ㧘߆ࠁ⁁ߩ㤛⊕⦡ߩ⚿᥏ߣߥࠆ߹ߢࠫࠛ

࠴࡞ࠛ࡯࠹࡞ߢᵞᵺߒߚߩߜࠈ೎ߒ㧘ࠛ࠲ࡁ࡯࡞

ࠃࠅౣ⚿᥏ߒߚ㧚෼㊂

11.5 g (35%).

ࡌࡦࠫ࡞

-4,6-O-

ࠕ࠾ࠪ࡝࠺ࡦ

-D-D-

ࠣ࡞ࠦࡇ࡜

ࡁࠪ࠼

(9)

¹³⁾

mp. 180-181 °C. [D]

²⁵D

+87° (c = 1.0, CHCl

3

).

D

-(+)-ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ࠍ↪޿ߚࠫࠛ࠴࡞

੝㋦ߦࠃࠆ⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕ ࡌࡦ࠭ࠕ࡞࠺ࡅ࠼߳ߩਇᢧઃട෻ᔕ

ࡈ࡟࡯ࡓ࠼࡜ࠗߒߚࠪࡘ࡟ࡦࠢߦࠕ࡞ࠧࡦ㔓࿐᳇

ਅ㧘ࠫࠢࡠࡠࡔ࠲ࡦ

(5 mL)

㧘ࡌࡦࠫ࡞

-2-

ࠕ࠮࠴࡞

ࠕࡒࡁ

-4,6-O-

ࠕ࠾ࠪ࡝࠺ࡦ

-2-

࠺ࠝࠠࠪ

-D-D-

ࠣ࡞ࠦ

ࡇ࡜ࡁࠪ࠼ (4) (0.25 mmol, 0.11 g) ࠍട߃ߡᡬᜈᓟ㧘

ࠫࠛ࠴࡞੝㋦ߩࡋࠠࠨࡦṁᶧ

(3.75 mmol, 3.75 mL)

ࠍṢਅߒ㧘ᰴ޿ߢࡌࡦ࠭ࠕ࡞࠺ࡅ࠼ (1.25 mmol,

0.13 g)

ࠍട߃ߚ㧚෻ᔕ⚳ੌᓟ㧘ࠫࠛ࠴࡞ࠛ࡯࠹࡞

ࠍട߃

1M-

Ⴎ㉄᳓ṁᶧߢᵞᵺߒߚᓟ㧘ή᳓⎫㉄ࡑ

ࠣࡀࠪ࠙ࡓߢੇ῎ߒ㧘ࠈㆊߒߚᓟ㧘ᷫ࿶ਅߢṁᇦ ࠍ⇐෰ߒ㧘ᱷ⇐ᶧࠍࠞ࡜ࡓࠢࡠࡑ࠻ࠣ࡜ࡈࠖ㧔ࡋ

ࠠࠨࡦ㧦㈶㉄ࠛ࠴࡞㧩

5 : 1

㧕ߦࠃࠅ♖⵾ߒߡ

1-

ࡈ ࠚ࠾࡞ࡊࡠࡄࡁ࡯࡞ࠍᓧ㧘GCߣ

HPLC㧘ᣓశశᐲ

⸘ߦࠃࠅಽᨆߒߚ㧚

⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕ

ࡈ࡟࡯ࡓ࠼࡜ࠗߒߚࠪࡘ࡟ࡦࠢߦࠕ࡞ࠧࡦ㔓࿐᳇

ਅ㧘ࠫࠢࡠࡠࡔ࠲ࡦ

5 mL㧘ࡌࡦࠫ࡞-2-ࠕ࠮࠴࡞ࠕ

ࡒࡁ

-4,6-O-

ࠕ࠾ࠪ࡝࠺ࡦ

-2-

࠺ࠝࠠࠪ

-D-D-

ࠣ࡞ࠦࡇ

࡜ࡁࠪ࠼ (4) (0.25 mmol, 0.11 g)㧘࠴࠲ࡦ㉄࠹࠻࡜

ࠗ࠰ࡊࡠࡇ࡞

(1.75 mmol, 0.49 g)

ࠍട߃ߡ

1

ᤨ㑆 ቶ᷷ߢᡬᜈᓟ㧘ࠫࠛ࠴࡞੝㋦ߩࡋࠠࠨࡦṁᶧ (3.75

mmol, 3.75 mL)

ࠍṢਅߒ㧘ᰴ޿ߢࡌࡦ࠭ࠕ࡞࠺ࡅ

࠼ (1.25 mmol, 0.13 g) ࠍട߃ߚ㧚෻ᔕ⚳ੌᓟ㧘ࠫ

ࠛ࠴࡞ࠛ࡯࠹࡞ࠍട߃㧝

M-

Ⴎ㉄᳓ṁᶧߢᵞᵺߒߚ ᓟ㧘ή᳓⎫㉄ࡑࠣࡀࠪ࠙ࡓߢੇ῎ߒ㧘ࠈㆊߒߚᓟ㧘

ᷫ࿶ਅߢṁᇦࠍ⇐෰ߒ㧘ᱷ⇐ᶧࠍࠞ࡜ࡓࠢࡠࡑ࠻

ࠣ࡜ࡈࠖ㧔ࡋࠠࠨࡦ㧦㈶㉄ࠛ࠴࡞㧩 5 : 1㧕ߦࠃࠅ

♖⵾ߒߡ

1-

ࡈࠚ࠾࡞ࡊࡠࡄࡁ࡯࡞ࠍᓧ㧘

GC

ߣ

HPLC㧘ᣓశశᐲ⸘ߦࠃࠅಽᨆߒߚ㧚

1-Phenyl-1-propanol: [D]

_D²⁵

+47° (c = 1.0, CHCl

₃

) (Lit.

¹⁴⁾

[D]

D25

+45.5° (c = 1.14, CHCl

3

) for (R)).

1-(2-Methoxyphenyl)-1-propanol: [D]

_D²⁵

+5.58° (c = 0.4, CHCl

3

) (Lit.

¹⁵⁾

[D]

D22

+27.6° (c = 2.03, CHCl

3

) for (R)).

1-(3-Methoxyphenyl)-1-propanol: [D]

_D²⁵

+28.85° (c =

0.9, CHCl

3

) (Lit.

¹⁶⁾

[D]

_D²⁵

+32.0° (c = 1.0, CHCl

3

) for (R)).

1-(4-Methoxyphenyl)-1-propanol: [D]

_D²⁵

+33.7° (c = 1.0, C

6

H

6

) (Lit.

¹⁷⁾

[D]

D22

+25.7° (c = 1, C

6

H

6

) for (R)).

1-(2-Chlorophenyl)-1-propanol: [D]

_D²⁵

+46.8° (c = 1.0, CHCl

3

) (Lit.

¹⁸⁾

+52.31° (c = 3.46, CHCl

3

) for (R)).

1-(4-Chlorophenyl)-1-propanol: [D]

_D²⁵

+34.9° (c = 1.4, CHCl

3

) (Lit.

¹⁴⁾

[D]

D25

+37.3° (c = 1.57, CHCl

3

) for (R)).

1-(1-Naphthyl)-1-propanol: [D]

_D²⁵

+25.8° (c = 1.0, CHCl

3

) (Lit.

¹⁸⁾

[D]

D25

+51.10° (c = 4.0, CHCl

3

) for (R)).

1-(2-Naphthyl)-1-propanol: [D]

_D²⁵

+30.1° (c = 2.0, CHCl

3

) (Lit.

¹⁶⁾

[D]

D25

31.7° (c = 1, CHCl

3

) for (R)).

1-Phenyl-1-penten-3-ol: [D]

_D²⁵

+31.1° (c = 2.2, CHCl

₃

) (Lit.

¹⁸⁾

[D]

D23

-6.6° (c = 3.20, CHCl

3

) for (S)).

㧚⚿ᨐߣ⠨ኤ

ࠠ࠻ࠨࡦ⺃ዉ૕ࠍ↪޿ࠆࠫࠛ࠴࡞੝㋦ߦࠃࠆ

⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕ

ࠠ࠻ࠨࡦ⺃ዉ૕ߩวᚑ

O X

R²O O

OR¹

n 1a chitin R¹ = H, R² = H, X = NHAc

1b chitosan R¹ = H, R² = H, X = NH₂ 1c 6-O-tritylchitosan R¹ = Tr, R² = H, X = NH₂ 1d N-benzylchitosan R¹ = H, R² = H, X = NHBn 1e N-benzyl-6-O-tritylchitosan R¹ = Tr, R² = H, X = NHBn 2a N-phthaloylchitosan R¹ = H, R² = H, X = phth

2b N-phthaloyl-3,6-di-O-acetylchitosan R¹ = R² = Ac, X = phth 2c N-phthaloyl-6-O-tritylchitosan R¹ = Tr, R² = H, X = phth 2d N-phthaloyl-6-O-phenylcarbamoylchitosan

R¹ = CONHPh, R² = H, X = phth 2e N-phthaloyl-6-O-dimethylcarbamoylchitosan

R¹ = CONMe₂, R² = H, X = phth Scheme 2. Chitosan derivatives.

ࠠ࠻ࠨࡦ (1b) ߪṁᇦߦਇṁߢ޽ࠆߚ߼㧘1b ߩ ൻቇୃ㘼ࠍ⹜ߺߚ

(Scheme 2)

㧚߹ߚ㧘ᓧࠄࠇߚൻ ቇୃ㘼ࠠ࠻ࠨࡦ߅ࠃ߮ 1a㧘1b ߩ᦭ᯏṁᇦߦኻߔ ࠆṁ⸃ᕈࠍ

Table 1

ߦ␜ߒߚ㧚

キトサン，D-(+)-グルコサミン誘導体を配位子とする金属錯体存在下でのジエチル亜鉛の芳香族アルデヒド類への触媒的不斉付加反応 117

߹ߕ 1b ߩࠕࡒࡁၮࠍࡈ࠲࡞ࠗࡒ࠼ൻߒߚ㧚N- ࡈ࠲ࡠࠗ࡞ࠠ࠻ࠨࡦ

(2a)

ߪ㜞෼₸ߢᓧࠄࠇ㧘ⶊ

⦡ߩ☳ᧃߢ޽ߞߚ㧚¹

H NMR

ࠬࡍࠢ࠻࡞ߢߪ

7.4- 7.8 ppm (phenyl)

ߩๆ෼߇㧘¹³

C NMR

ࠬࡍࠢ࠻࡞ߢ ߪࡈ࠲࡞ࠗࡒ࠼ၮߩࠞ࡞ࡏ࠾࡞὇⚛ߦࠃࠆ

160.8-

168.1 ppm

ߩๆ෼߅ࠃ߮

IR

ࠬࡍࠢ࠻࡞ߢߪ

1700

cm

^-1 ߩๆ෼߇⹺߼ࠄࠇ㧘ࡈ࠲࡞ࠗࡒ࠼ၮߩሽ࿷߇

⏕⹺ߐࠇߚ㧚2a ߪࡇ࡝ࠫࡦߦนṁߢ޽ߞߚ㧚 2a ߩ

3,6

૏ߩ᳓㉄ၮߩࠕ࠮࠴࡞ൻࠍ⹜ߺߚ㧚N- ࡈ࠲ࡠࠗ࡞-3,6-O-ࠫࠕ࠮࠴࡞ࠠ࠻ࠨࡦ (2b) ߪ㧘 ࡇ࡝ࠫࡦਛ㧘ή᳓㈶㉄ߣߩ෻ᔕߦࠃࠅᓧࠄࠇߚ㧚

13

C NMR

ࠬࡍࠢ࠻࡞ߦࠃࠅ᳓㉄ၮ߇ࠕ࠮࠴࡞ൻߐ

ࠇߚߎߣ߇⏕⹺ߐࠇ㧘Ⴎൻࡔ࠴࡟ࡦߥߤߦนṁߣ ߥߞߚ㧚

ߟ߉ߦ

6

૏ߩ᳓㉄ၮߦ࠻࡝࠴࡞ၮࠍዉ౉ߒߚN- ࡈ࠲ࡠࠗ࡞-6-O-࠻࡝࠴࡞ࠠ࠻ࠨࡦ (2c) ߩวᚑࠍ ⴕߞߚ㧚2a ࠍࡇ࡝ࠫࡦਛ㧘Ⴎൻ࠻࡝࠴࡞ߣ૞↪ߐ ߖࠆߣ 2c ߇ᓧࠄࠇߚ㧚

2c ߩࡈ࠲࡞ࠗࡒ࠼ၮࠍࡅ࠼࡜ࠫࡦ৻᳓๺‛ߢ ട᳓ಽ⸃ߒߚ㧚↢ᚑ‛ߩ

IR

ࠬࡍࠢ࠻࡞ߢߪࡈ࠲࡞

ࠗࡒ࠼ၮߦ↱᧪ߔࠆ

1700 cm

^-1

(C=O)

ߩๆ෼߇ᶖᄬ ߒߡ߅ࠅ㧘¹

H NMR

ࠬࡍࠢ࠻࡞ߢ߽ࡈ࠲࡞ࠗࡒ࠼

ၮߦᏫዻߔࠆࡈࠚ࠾࡞ၮߩๆ෼߇ᶖᄬߒߡ޿ࠆߎ ߣ߆ࠄട᳓ಽ⸃ߐࠇ㧘

6-O-

࠻࡝࠴࡞ࠠ࠻ࠨࡦ

(1c)

߇ᓧࠄࠇߚߣ⏕⹺ߐࠇߚ㧚

1b ߅ࠃ߮ 1c ߩࠕࡒࡁၮ߳ߩࡌࡦࠫ࡞ၮߩዉ౉

ࠍⴕߞߚ㧚1b ߣ⥇ൻࡌࡦࠫ࡞ߩ෻ᔕߢ N-ࡌࡦࠫ

࡞ࠠ࠻ࠨࡦ (1d) ࠍᓧߚ㧚߹ߚ㧘1c ߦࡌࡦ࠭ࠕ࡞

࠺ࡅ࠼ࠍቶ᷷ߢ

24

ᤨ㑆෻ᔕߐߖߡᓧࠄࠇߚࠪ࠶

ࡈႮၮࠍ

DMF

ਛߢ᳓⚛ൻࡎ࠙⚛࠽࠻࡝࠙ࡓㆶర ߒߚ㧚

IR

ࠬࡍࠢ࠻࡞ߢㆶర೨ߩࠪ࠶ࡈႮၮߦࠃ ࠆๆ෼߇ᶖᄬߒߡ޿ࠆߎߣ߆ࠄ N-ࡌࡦࠫ࡞

-6-O-

࠻

࡝࠴࡞ࠠ࠻ࠨࡦ

(1e)

ߢ޽ࠆߎߣ߇⏕⹺ߐࠇߚ㧚 N-ࡈ࠲ࡠࠗ࡞-6-O-ࡈࠚ࠾࡞ࠞ࡞ࡃࡕࠗ࡞ࠠ࠻ࠨ ࡦ

(2d)

߅ࠃ߮ N-ࡈ࠲ࡠࠗ࡞

-6-O-

ࠫࡔ࠴࡞ࠞ࡞ࡃ ࡕࠗ࡞ࠠ࠻ࠨࡦ

(2e)

ߪ㧘ߘࠇߙࠇ 2a ࠍࡇ࡝ࠫ

ࡦਛ㧘ࠗ࠰ࠪࠕࡦ㉄ࡈࠚ࠾࡞߹ߚߪႮൻࠫࡔ࠴࡞

ࠞ࡞ࡃࡕࠗ࡞ࠍ

80

°Cߢ

24

ᤨ㑆૞↪ߐߖߡᓧߚ㧚

2d ߢߪ ¹³

C NMR

ࠬࡍࠢ࠻࡞ߩࠞ࡞ࡃࡕࠗ࡞ၮߩ

ࠞ࡞ࡏ࠾࡞὇⚛ߦࠃࠆๆ෼

152.7, 153.6 ppm

ߣࡈࠚ

࠾࡞ၮߩๆ෼

118.3-123.5 ppm

㧘

IR

ࠬࡍࠢ࠻࡞ߩ

1752, 1602 cm

^-1

(C=O)

ߩๆ෼ࠃࠅ᳓㉄ၮ߇ࡈࠚ࠾

࡞ࠞ࡞ࡃࡕࠗ࡞ൻߐࠇߚߎߣ߇㧘߹ߚ㧘2e ߢߪ

13

C NMR

ࠬࡍࠢ࠻࡞ߩࠞ࡞ࡏ࠾࡞὇⚛ߦࠃࠆๆ෼

(164.1 ppm)

㧘ࡔ࠴࡞ၮ὇⚛ߩๆ෼

(18.4 ppm)

ߣ

IR

ࠬࡍࠢ࠻࡞ߩࠞ࡞ࡃࡕࠗ࡞ၮߦ↱᧪ߔࠆ

1700 cm

^-1 ߩๆ෼ࠃࠅ᳓㉄ၮ߇ࠫࡔ࠴࡞ࠞ࡞ࡃࡕࠗ࡞ൻ ߐࠇߚߎߣ߇⏕⹺ߐࠇߚ㧚ࠠ࠻ࠨࡦ⺃ዉ૕ 2d㧘2e ߪ㧘3 ૏ߩ᳓㉄ၮ߽⟎឵ߐࠇࠆน⢻ᕈ߇޽ࠆ߇㧘

┙૕⊛ߦ

3

૏ߩ᳓㉄ၮߪ⟎឵ߐࠇߦߊ޿ߎߣ߆ࠄ

6

૏ߩ᳓㉄ၮߩߺ⟎឵ߐࠇߡ޿ࠆߣ⠨߃ࠄࠇࠆ㧚 ߎࠇࠄߪฦ⒳᦭ᯏṁᇦߦนṁߣߥߞߚ㧚

Table 1. Solubility of chitosan derivatives.^a) Modified

chitosan

DMF DMSO Pyridine CHCl3 CH2Cl2 Toluene

1a – – – – – – 1b – – – – – – 1c + + + ± – – 1d + + + – – – 1e + + + + + – 2a + + + – – – 2b + + + + + – 2c + + + + ± – 2d + + + + + – 2e + + + ± + – a) (+) = soluble, (±) = partially soluble or swelled, (–) = insoluble, 10 mg of sample in 2 mL of solvent at room temperature.

ࠠ࠻ࠨࡦ⺃ዉ૕ࠍ㈩૏ሶߣߔࠆࠫࠛ࠴࡞੝

㋦ߦࠃࠆ⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕ

ࠠ࠴ࡦ㧘ࠠ࠻ࠨࡦ߅ࠃ߮ࠠ࠻ࠨࡦ⺃ዉ૕ߪ㜞ಽ ሶ૕ߢ޽ࠆߎߣ߆ࠄ㧘ṁᇦߦኻߔࠆṁ⸃ᐲߩᏅࠍ

೑↪ߒ㧘෻ᔕᷙว‛߆ࠄߩಽ㔌㧘࿁෼㧘ౣ೑↪߇ ኈᤃߢ޽ࠆ㧚ࠠ࠻ࠨࡦࠍਇᢧ⸅ᇦ෻ᔕߦ↪޿ߚ଀

ߪ㧘⵬㉂⚛࠾ࠦ࠴ࡦࠕࡒ࠼ࠕ࠺࠾ࡦࠫ࠿ࠢ࡟ࠝ࠴

࠼ (NAD) ߩㆶర૕ߢ޽ࠆ

NADH

ࠍࡕ࠺࡞ߣߒߚ ਇᢧㆶర෻ᔕ ¹⁹⁾ ߿ਇᢧࠪࠕࡁൻ ²⁰⁾ ߇⹜ߺࠄࠇߡ

޿ࠆߩߺߢ޽ࠆ㧚ߒ߆ߒ㧘ߎࠇࠄߩ෻ᔕߦ߅޿ߡ ߪ㜞޿ࠛ࠽ࡦ࠴ࠝㆬᛯᕈ߇ᓧࠄࠇߡ޿ߥ޿㧚ߘߎ ߢ㧘὇⚛㧙὇⚛⚿ว↢ᚑ෻ᔕߢ޽ࠆࠫࠕ࡞ࠠ࡞੝

㋦ߩࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕߦࠃࠆశቇᵴ

119

ᕈ╙ੑ⚖ࠕ࡞ࠦ࡯࡞ߩวᚑ⸅ᇦߣߒߡ੹࿁วᚑߒ ߚࠠ࠻ࠨࡦ⺃ዉ૕ࠍᬌ⸛ߒߚ

(Eq. 1)

㧚

O

H + Et2Zn

chitosan derivatives OH CH2Cl2

(1)

ࠠ࠻ࠨࡦ⺃ዉ૕ߩ⸅ᇦലᨐ

ࠠ࠴ࡦ㧘ࠠ࠻ࠨࡦ߅ࠃ߮⒳ޘߩࠠ࠻ࠨࡦ⺃ዉ૕

ࠍ↪޿ߚਇᢧࠕ࡞ࠠ࡞ൻ෻ᔕߩ⚿ᨐࠍ

Table 2

ߦ␜

ߒߚ㧚⸅ᇦߣߒߡࠠ࠴ࡦ

(1a)

߽ߒߊߪࠠ࠻ࠨࡦ

(1b)

ࠍ↪޿ߚ႐ว㧘⧯ᐓ෻ᔕ߇ㅴⴕߒߚ߇㧘┙૕

ㆬᛯᕈߪ␜ߐߥ߆ߞߚ

(Entries 2 and 3)

㧚ࠠ࠴ࡦ㧘

ࠠ࠻ࠨࡦ߇෻ᔕ♽ߦਇṁߢ޽ࠆߚ߼߶ߣࠎߤ෻ᔕ ߦነਈߒߥ߆ߞߚߚ߼ߣ⠨߃ࠄࠇࠆ㧚

ߘߎߢ㧘ࠕࡒࡁၮߦࡌࡦࠫ࡞ၮࠍዉ౉ߒߚࠠ࠻

ࠨࡦ⺃ዉ૕ࠍ↪޿ߚਇᢧࠕ࡞ࠠ࡞ൻ෻ᔕߦߟ޿ߡ ᬌ⸛ߒߚ㧚N-ࡌࡦࠫ࡞ࠠ࠻ࠨࡦ (1d) ߢߪ㧘෻ᔕ ߪㅴⴕߒߚ߇㧘↢ᚑ‛ߪ࡜࠮ࡒ૕ߢ޽ߞߚ

(Entry

5)㧚ߒ߆ߒ㧘6

૏ߦ࠻࡝࠴࡞ၮࠍዉ౉ߒߚ 1e ࠍ↪

޿ߚߣߎࠈㆬᛯᕈ߇

16%

ee ߣߥߞߚ

(Entry 6)

㧚

࠻࡝࠴࡞ၮ߇┙૕⊛ᓇ㗀ࠍ෸߷ߒߡ޿ࠆߎߣ㧘ߥ ࠄ߮ߦ᦭ᯏṁᇦߦኻߒߡṁߌ߿ߔߊߥߞߚߎߣ߇

ࠛ࠽ࡦ࠴ࠝㆬᛯᕈࠍ␜ߒߚᄢ߈ߥⷐ࿃ߢߪߥ޿߆ ߣ⠨߃ࠄࠇࠆ㧚߹ߚ㧘ㆆ㔌ߩࠕࡒࡁၮࠍᜬߟ 1c ߢߪ㧘ోߊ෻ᔕ߇ㅴⴕߒߥ߆ߞߚ (Entry 4)㧚෻ᔕ ၮ⾰ߩࡌࡦ࠭ࠕ࡞࠺ࡅ࠼߇ࠕࡒࡁၮߣ෻ᔕߒ㧘ࠪ

࠶ࡈႮၮࠍᒻᚑߒߡᶖ⾌ߐࠇࠆߚ߼ߣ⠨߃ࠄࠇࠆ㧚

ᰴߦ㧘N-ࡈ࠲ࡠࠗ࡞ࠠ࠻ࠨࡦ

(2a)

ࠍ⸅ᇦߦ↪

޿ߚߣߎࠈ㧘෼₸ 36㧑ߢ෻ᔕ߇ㅴⴕߒ㧘߹ߚశቇ

෼₸ߪ

32% ee (R)

ߣߥߞߚ

(Entry 7)

㧚ࠫࠢࡠࡠࡔ

࠲ࡦߦนṁߥ 2b ࠍ↪޿ߚߣߎࠈ㧘෻ᔕ෼₸ߪૐ ਅߒߚ߇┙૕ㆬᛯᕈߪ

44%

ee ߣะ਄ߒߚ

(Entry

8)㧚ᰴߦ㧘ࠃࠅ┙૕⊛ߦ߆ߐ㜞޿࠻࡝࠴࡞ၮࠍ 6

૏ߦዉ౉ߒߚ 2c ࠍ⸅ᇦߣߒߡ↪޿ߚߣߎࠈ㧘෻

ᔕ෼₸

69%㧘శቇ෼₸ 56% ee

ߣ⦟ᅢߥ⚿ᨐ߇ᓧࠄ

ࠇߚ

(Entry 9)

㧚㈩૏ᕈ⟎឵ၮߢ޽ࠆࡈࠚ࠾࡞ࠞ࡞

ࡃࡕࠗ࡞ၮ㧘ࠫࡔ࠴࡞ࠞ࡞ࡃࡕࠗ࡞ၮࠍዉ౉ߒߚ 2d㧘2e ࠍ↪޿ߚߣߎࠈ㧘2d ߢߪㆬᛯᕈߪ㜞޿߇㧘

෻ᔕᕈߪૐߊߥߞߚ㧚⚿ᨐߣߒߡ N-ࡈ࠲ࡠࠗ࡞

-6-

O-࠻࡝࠴࡞ࠠ࠻ࠨࡦ

(2c)

ࠍ↪޿ߚߣ߈߇෻ᔕᕈ㧘

┙૕ㆬᛯᕈߣ߽ᦨ߽⦟ᅢߥ⚿ᨐࠍਈ߃ߚ㧚

Table 2. Asymmetric addition of diethylzinc to benzaldehyde catalyzed by chitin, chitosan and modified chitosans.^a)

Entry Catalyst

1-Phenyl-1-propanol Yield

( % )^b)

E.e. ^c)

(% ee) Config.^d)

1 None 0 㧙 㧙

2 1a trace racemic 㧙

3 1b 5 racemic 㧙

4 1c trace racemic 㧙

5 1d 54 racemic 㧙

6 1e 66 16 R

7 2a 36 32 R

8 2b 27 44 R

9 2c 69 56 R

10 2d 42 55 R

11 2e 86 45 R

a) Reaction conditions: benzaldehyde (1.0 mmol), diethylzinc 1.0 M solution in hexane (3.4 mmol, 3.4 mL), catalyst (0.5 mmol / 1 unit), dichloromethane (10 mL), 0 °C, 24 h. b) Determined by GLC.

c) Determined by HPLC. (DAICEL CHIRALCEL OD-H, n-hexane / i-PrOH = 98 / 2, 0.5 mL/min, uv 254 nm). d) See experimental section.

෻ᔕ᧦ઙߩᬌ⸛

N-ࡈ࠲ࡠࠗ࡞

-6-O-

࠻࡝࠴࡞ࠠ࠻ࠨࡦ

(2c)

ࠍ↪

޿ߡฦ⒳෻ᔕ᧦ઙߩᬌ⸛ࠍⴕߞߚ

(Table 3)

㧚 ਇᢧ⸅ᇦ෻ᔕߢߪ㧘⸅ᇦߩ㊂߇෻ᔕᕈ㧘┙૕ㆬ

ᛯᕈߦᄢ߈ߥᓇ㗀ࠍ෸߷ߔ㧚ߘߎߢ⸅ᇦ㊂ߩലᨐ ߦ ߟ ޿ ߡ ᬌ ⸛ ߒ ߚ 㧚 ⸅ ᇦ ㊂ ߇ ၮ ⾰ ߦ ኻ ߒ ߡ

50

mol%

ߩᤨ㧘ᦨ߽㜞޿శቇ෼₸ࠍ␜ߒߚ

(Entries

1-4, and 7)

㧚

-78

°C㧘

-30

°C ߢߪ߶ߣࠎߤ෻ᔕ߇ㅴ߹ߥ߆ߞ ߚ߇㧘෻ᔕ᷷ᐲ߇

0

°C߅ࠃ߮ቶ᷷ߢߪ㧘෻ᔕ෼₸

ߣశቇ෼₸ߣ߽ߦᅢ⚿ᨐࠍਈ߃ߚ (Entries 5-8)㧚 ṁᇦߣߒߡߪࠫࠢࡠࡠࡔ࠲ࡦ߇ᦨ߽⦟޿⚿ᨐࠍ ਈ߃ߚ

(Entries 7, 9, and 10)

㧚2c ߩṁ⸃ᕈ߇┙૕ㆬ

ᛯᕈߦᓇ㗀ࠍਈ߃ߡ޿ࠆߣ⠨߃ࠄࠇࠆ㧚

ࠫࠛ࠴࡞੝㋦ߣࡌࡦ࠭ࠕ࡞࠺ࡅ࠼ߩỚᐲࠍ㜞ߊ ߔࠆߣㆬᛯᕈߩะ਄߇⷗ࠄࠇߚ

(Entries 7 and 11)

㧚 キトサン，D-(+)-グルコサミン誘導体を配位子とする金属錯体存在下でのジエチル亜鉛の芳香族アルデヒド類への触媒的不斉付加反応

Table 3. The effects of reaction conditions in the asymmetric addition of diethylzinc to benzaldehyde.^a)

Entry 2c (mol%)

Temp

(°C) Solv㧚

1-Phenyl-1- propanol Yield (%)^b)

% ee^c) (config.)

1 10 0 CH2Cl2 77 34 (R)

2 30 0 CH2Cl2 61 49 (R)

3 70 0 CH2Cl2 84 51 (R)

4 100 0 CH2Cl2 73 50 (R)

5 50 -78 CH2Cl2 trace 㧙 6 50 -30 CH2Cl2 trace 㧙

7 50 0 CH2Cl2 69 56 (R)

8 50 r.t. CH2Cl2 69 54 (R) 9 50 0 C6H5Me 77 38 (R) 10 50 0 n-C6H14 45 11 (R) 11^d) 50 0 CH2Cl2 46 61 (R) a) Reaction conditions: benzaldehyde (1.0 mmol), diethylzinc 1.0 M solution in hexane (3.4 mmol, 3.4 mL), solvent (10 mL), 24 h. b) Determined by GLC. c) Determined by HPLC. (DAICEL CHIRALCEL OD-H, n-Hexane / i-PrOH = 98 / 2, 0.5 mL / min, uv 254 nm). d) Reaction conditions: benzaldehyde (5 mmol), diethylzinc 1.0 M solution in hexane (6.0 mL), CH2Cl2 (10 mL), 6 h.

એ਄ߩ⚿ᨐߪᰴߩࠃ߁ߦ߹ߣ߼ࠄࠇࠆ㧚

⦟ᅢߥ෻ᔕ෼₸ࠍᓧࠆߚ߼ߦߪ㧘

6

૏ߩ⟎឵ၮ㧘

⓸⚛਄ߩ⟎឵ၮߥࠄ߮ߦ

3

૏ߩ᳓㉄ၮߩሽ࿷߇ᔅ ⷐߢ޽ࠆ㧚߹ߚ㧘శቇ෼₸߽᦭ᯏṁᇦߦนṁߥࠠ

࠻ࠨࡦ⺃ዉ૕ߢ㜞ߊߥߞߚ㧚⚿ᨐߣߒߡ 2c ߇ᦨ

߽᦭ലߢ޽ߞߚ߇㧘ࠃࠅ㜞޿శቇ෼₸߇ᓧࠄࠇߥ

޿ℂ↱ߣߒߡ㧘ࠠ࠻ࠨࡦ⺃ዉ૕ 2c ߇㜞ಽሶߢ޽

ࠆߚ߼㧘ߘߩ⴫㕙਄ߦࠫࠛ࠴࡞੝㋦߇ਇⷙೣߦ⚿

วߔࠆߎߣߢ㧘┙૕ㆬᛯᕈߩૐ޿෻ᔕ߽ㅴⴕߔࠆ ߆ࠄߢ޽ࠆߣ⠨߃ࠄࠇࠆ㧚

ฦ⒳⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃ߩᬌ⸛

⧐ 㚅 ᣖ ࠕ ࡞ ࠺ ࡅ ࠼ ߩ ⟎ ឵ ၮ ല ᨐ ࠍ ᬌ ⸛ ߒ ߚ

(Table 4)

㧚ߘߩ⚿ᨐ㧘⟎឵ၮ߇ࡄ࡜૏㧘ࡔ࠲૏㧘

ࠝ࡞࠻૏ߣࠕ࡞࠺ࡅ࠼ၮߦㄭߊߥࠆߦᓥߞߡࠛ࠽

ࡦ࠴ࠝㆬᛯᕈ߇ะ਄ߒߚ

(Entries 2-6)

㧚㔚ሶ⊛ലᨐ ߪ޽߹ࠅߥ޿ߣ⠨߃ࠄࠇࠆ㧚߹ߚ㧘

2-

࠽ࡈ࠻ࠕ࡞

࠺ࡅ࠼ߦᲧߴ

1-

࠽ࡈ࠻ࠕ࡞࠺ࡅ࠼ߩᣇ߇

66% ee

ߣ ࠃࠅ㜞޿ࠛ࠽ࡦ࠴ࠝㆬᛯᕈࠍ␜ߒߚ (Entries 7 and

8)

㧚᩵⊹ࠕ࡞࠺ࡅ࠼

(Entry 9)

ߢߪ㧘෻ᔕ෼₸ߪ㜞

޿߽ߩߩ┙૕ㆬᛯᕈߪ␜ߐߥ߆ߞߚ㧚

Table 4. Asymmetric addition of diethylzinc to various aldehydes.^a)

Entry Aldehydes (RCHO) R =

Yield (%)^b)

% ee^c) (config.)

1 C6H5 69 54 (R)

2 2-CH3OC6H4 75 54 (R)

3 3-CH3OC6H4 71 42 (R)

4 4-CH3OC6H4 53 32 (R)

5 2-ClC6H4 75 57 (R)

6 4-ClC6H4 62 53 (R)

7 1-Naphthyl 49 66 (R)

8 2-Naphthyl 46 53 (R)

9 C6H5CH=CH 72 racemic

a) Aldehyde (1.0 mmol), diethylzinc 1.0 M solution in hexane (3.4 mmol, 3.4 mL), catalyst (2c) (0.5 mmol/1unit), CH2Cl2 (10 mL), 0 °C, Time, 24 h. b) Isolated yields. c) See experimental section.

D

-(+)-

ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ࠍ↪޿ࠆࠫࠛ࠴࡞

੝㋦ߦࠃࠆࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕ ࠠ࠻ࠨࡦߩ㛽ᩰࠍߥߔ D

-(+)-

ࠣ࡞ࠦࠨࡒࡦߪ㧘 㕖Ᏹߦ቟ଔߢ౉ᚻ߇ኈᤃߢ޽ࠅ㧘ਇᢧ὇⚛ࠍᜬߜ㧘 ࠕࡒࡁၮ㧘᳓㉄ၮࠍ᦭ߔࠆߎߣ߆ࠄశቇᵴᕈ㈩૏

ሶߣߒߡᦼᓙߐࠇࠆ㧚ߘߎߢ㧘D

-(+)-ࠣ࡞ࠦࠨࡒࡦ

ߣߘߩ⺃ዉ૕ࠍ㈩૏ሶߣߒߡ↪޿ߚ⧐㚅ᣖࠕ࡞࠺

ࡅ࠼㘃߳ߩࠫࠛ࠴࡞੝㋦ߦࠃࠆਇᢧઃട෻ᔕ߳ߩ

⸅ᇦലᨐߦߟ޿ߡᬌ⸛ߒߚ²¹⁾㧚

D

-(+)-

ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ߩวᚑ

D

-(+)-ࠣ࡞ࠦࠨࡒࡦߪ᳓߅ࠃ߮ࡔ࠲ࡁ࡯࡞ߩߺ

ߦߒ߆ṁ⸃ߒߥ޿㧚ṁ⸃ᕈߩะ਄ߣ┙૕⊛ⅣႺߩ

᭴▽ࠍ⋡⊛ߣߒߡ⺃ዉ૕ൻࠍ⹜ߺߚ (Scheme 3)㧚

࠽࠻࡝࠙ࡓࡔ࠻ࠠࠪ࠼ሽ࿷ਅ㧘D

-(+)-

ࠣ࡞ࠦࠨ ࡒࡦႮ㉄Ⴎ (3) ߣή᳓㈶㉄ߣ෻ᔕߐߖߡࠕ࠮࠻ࠕ ࡒ࠼ၮߦᄌ឵ߒ㧘ᰴߦ

1

૏ߩࠕࡁࡔ࡝࠶ࠢ὇⚛਄

ߩ᳓㉄ၮࠍࡌࡦࠫ࡞ࠕ࡞ࠦ࡯࡞ߢࠣ࡞ࠦࠪ࠼⚿ว ߦߒߡࡌࡦࠫ࡞

-2-

ࠕ࠮࠴࡞ࠕࡒ࠼

-2-

࠺ࠝࠠࠪ

-D-

D

-

ࠣ࡞ࠦࡇ࡜ࡁࠪ࠼ (4) ࠍวᚑߒߚ㧚ߐࠄߦ㧘4,6

૏ߩ᳓㉄ၮࠍࠕ࠾ࠪ࡝࠺ࡦൻߒߚࡌࡦࠫ࡞

-2-

ࠕ࠮

࠴࡞ࠕࡒ࠼-4,6-O-ࠕ࠾ࠪ࡝࠺ࡦ-2-࠺ࠝࠠࠪ-D-D

-ࠣ

࡞ࠦࡇ࡜ࡁࠪ࠼

(6)

㧘ࡌࡦࠫ࡝࠺ࡦൻߒߚࡌࡦࠫ

࡞-2-ࠕ࠮࠴࡞ࠕࡒ࠼-4,6-O-ࡌࡦࠫ࡝࠺ࡦ-2-࠺ࠝࠠ

ࠪ

-D-

D

-

ࠣ࡞ࠦࡇ࡜ࡁࠪ࠼

(7)

ࠍวᚑߒߚ㧚߹ߚ㧘

6

૏ߦ፾㜞޿࠻࡝࠴࡞ၮࠍዉ౉ߒߚࡌࡦࠫ࡞-2-ࠕ

121

࠮࠴࡞ࠕࡒ࠼

-6-O-

࠻࡝࠴࡞

-2-

࠺ࠝࠠࠪ

-D-

D

-

ࠣ࡞ࠦ

ࡇ࡜ࡁࠪ࠼

(5)

ࠍ㧘߹ߚ㧘ࠕ࠮࠻ࠕࡒ࠼ၮߩᓇ㗀 ࠍ⺞ߴࠆߚ߼ߦࡔ࠴࡞

-4,6-O-

ࠕ࠾ࠪ࡝࠺ࡦ

-D-

D

-

ࠣ

࡞ࠦࡇ࡜ࡁࠪ࠼ (8)߿ࡌࡦࠫ࡞-4,6-O-ࠕ࠾ࠪ࡝࠺

ࡦ

-D-

D

-

ࠣ࡞ࠦࡇ࡜ࡁࠪ࠼

(9)

ࠍวᚑߒߚ㧚

O

X HO R³O

OR¹ R²O

3 R¹ = R² = R³ = H, X = NH₃Cl 4 R¹ = Bn, R² = R³ = H, X = NHAc 5 R¹ = Bn, R² = Tr, R³ = H, X = NHAc 6 R¹ = Bn, R²-R³ = CHC₆H₄OMe(4), X = NHAc 7 R¹ = Bn, R²-R³ = CHC₆H₅, X = NHAc 8 R¹ = Me, R²-R³ = CHC₆H₄OMe(4), X = OH 9 R¹ = Bn, R²-R³ = CHC₆H₄OMe(4), X = OH

Scheme 3. D-Glucosamine derivatives.

D

-(+)-ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ࠍ↪޿ߚࠫࠛ࠴

࡞੝㋦ߩ⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩਇᢧઃട෻ᔕ

D

-(+)-

ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ߩ⸅ᇦലᨐ

O

H + Et2Zn

glucosamine derivatives

OH CH₂Cl₂

(2)

Table 5. Asymmetric addition of diethylzinc.^a㧕

Entry Ligand Ti(O-i-Pr)4

equiv.^b)

1-Phenyl-1-propanol Yield

(%)^c)

E.e.

(% ee)^d) Config.^e)

1 3 none 16 racemic 㧙

2 4 none 25 racemic 㧙

3 5 none 2 racemic 㧙

4 6 none 39 racemic 㧙

5 3 1.4 10 racemic 㧙

6 4 1.4 70 41 R

7 5 1.4 65 33 S

8 6 1.4 85 88 R

9 7 1.4 86 91 R

10 8 1.4 13 33 S

11 9 1.4 71 31 S

a) Reaction conditions: benzaldehyde : Ligand : Et2Zn = 1.0 : 0.2 : 3.0 (molar ratio), r.t., 24 h. b) Based on aldehyde. c) Determined by GLC. d) DAICEL CHIRALCEL OB, Hexane / i-PrOH = 90 / 10, 0.5 mL / min, uv 254 nm. e) See experimental section.

ࠫࠛ࠴࡞੝㋦ߩࡌࡦ࠭ࠕ࡞࠺ࡅ࠼߳ߩਇᢧઃട

෻ᔕߦ߅޿ߡ㧘਄⸥ߢᓧࠄࠇߚ

3

㨪

9

ߩ⸅ᇦലᨐ ߦߟ޿ߡᬌ⸛ߒߚ

(Eq. 2, Table 5)

㧚

D

-(+)-ࠣ࡞ࠦࠨࡒࡦႮ㉄Ⴎ (3)

ࠍ↪޿ߚߣߎࠈ㧘

↢ᚑ‛ߩ෼₸ߪૐߊ㧘߆ߟ࡜࠮ࡒ૕ߢ޽ߞߚ㧚ߐ ࠄߦ㧘ൻว‛ 4㧘5㧘6 ࠍ↪޿ߡ෻ᔕࠍ⹜ߺߚ㧚ߒ ߆ߒ㧘෻ᔕߪㅴⴕߒߚ߇෼₸߇ᖡߊ㧘࡜࠮ࡒ૕߇ ᓧࠄࠇߚ

(Entries 1-4)

㧚

৻ᣇ㧘࠴࠲ࡦ

(IV)

࠹࠻࡜ࠗ࠰ࡊࡠࡐࠠࠪ࠼ࠍᷝ

ടߔࠆߣ㧘ઃട෻ᔕ߇ടㅦߒ㧘ਇᢧ෼₸ߦ߽ᓇ㗀 ߔࠆߎߣ߇ႎ๔ߐࠇߡ޿ࠆ

(Scheme 4)

^22,23)㧚

O

H + Et2Zn ligand , Ti(O-iPr)₄

OH

O O

Tf N N Tf Ti(O-i-Pr)2 Ti(O-i-Pr)2

CH2Cl2

Scheme 4. Addition of diethylzinc to benzaldehyde.

ߘߎߢ㧘࠴࠲ࡦ

(IV)

࠹࠻࡜ࠗ࠰ࡊࡠࡐࠠࠪ࠼ࠍ

ᷝടߒߡ෻ᔕࠍⴕߞߚ (Entries 5-11)㧚 D

-(+)-ࠣ࡞

ࠦࠨࡒࡦႮ㉄Ⴎ

(3)

ߢߪ෻ᔕߪ߶ߣࠎߤㅴⴕߒߥ ߆ߞߚ߇㧘ൻว‛ 4 ߢߪ෼₸

70%㧘శቇ෼₸

41%

ee (R) ߣ⦟ᅢߥ⚿ᨐ߇ᓧࠄࠇߚ㧚ࠃࠅ፾㜞޿

࠻࡝࠴࡞ၮࠍዉ౉ߒߚ 5 ߢߪ෼₸

65%㧘శቇ෼₸

33%

eeߢ⛘ኻ㈩⟎߇ S૕ߩ߽ߩ߇ᓧࠄࠇߚ㧚

4

૏ ߣ

6

૏ߩ᳓㉄ၮࠍࠕ࠮࠲࡯࡞ൻߒߚ 6 ߢߪ෼₸

85%

㧘శቇ෼₸

88%

ee (R) ߣ㜞޿ൻቇ෼₸ߣࠛ࠽

ࡦ࠴ࠝㆬᛯᕈࠍ␜ߒߚ㧚

ਇᢧࠍ⺃ዉߔࠆ┙૕⊛ߥⅣႺࠍᲧセߔࠆߚ߼ߦ

4,6

૏ߩ᳓㉄ၮࠍࡌࡦ࠭ࠕ࡞࠺ࡅ࠼ߢࠕ࠮࠲࡯࡞ൻ ߒߚ 7 ࠍ↪޿ߚ߇㧘⚿ᨐߪ 6 ࠍ↪޿ߚᤨߣᄌࠊ ࠄߕ㧘ࡔ࠻ࠠࠪၮߩᓇ㗀ߪߥ޿ߎߣ߇ಽ߆ߞߚ㧚

ᰴߦࠕ࠮࠻ࠕࡒ࠼ၮߩᓇ㗀ࠍ⺞ߴࠆߚ߼ߦ Į-D

-

ࠣ

࡞ࠦࠪ࠼⺃ዉ૕ߩ 8 ߣ 9 ࠍ෻ᔕߦ↪޿ߚ㧚ߘߩ

⚿ᨐ㧘⛘ኻ㈩⟎߇ S ૕ߢૐ޿┙૕ㆬᛯᕈߣߥࠅ㧘 ࠕ࠮࠻ࠕࡒ࠼ၮ߇ㆬᛯᕈߦᓇ㗀ߒߡ޿ࠆߎߣ߇ࠊ ߆ߞߚ㧚߹ߚ㧘ࠣ࡞ࠦࠪ࠼ㇱ૏ߩࡌࡦࠫ࡞ၮߣࡔ

࠴࡞ၮࠍᲧߴࠆߣࡔ࠴࡞ၮߢߪ෼₸߇ૐਅߒߚ.

キトサン，D-(+)-グルコサミン誘導体を配位子とする金属錯体存在下でのジエチル亜鉛の芳香族アルデヒド類への触媒的不斉付加反応

ߎߩࠃ߁ߦ㧘࠴࠲ࡦ

(IV)

࠹࠻࡜ࠗ࠰ࡊࡠࡐࠠࠪ

࠼ߣ㈩૏ሶ 6 ߿ 7 ߩ೑↪߇⦟޿⚿ᨐࠍਈ߃ߚߩ ߢ㧘ߎࠇࠄࠍ↪޿ߡ෻ᔕ᧦ઙߩᬌ⸛ߥࠄ߮ߦฦ⒳

⧐㚅ᣖࠕ࡞࠺ࡅ࠼ߣߩ෻ᔕࠍⴕߞߚ㧚

෻ᔕ᧦ઙߩᬌ⸛

Cṁᇦലᨐ

(Table 6)

ṁᇦߣߒߡࠫࠢࡠࡠࡔ࠲ࡦࠍ↪޿ߚߣ߈㧘෼₸

86%

㧘ࠛ࠽ࡦ࠴ࠝㆬᛯᕈ

88% ee

ߣᦨ߽㜞޿⚿ᨐ ߇ᓧࠄࠇߚ߇㧘࠻࡞ࠛࡦ߿

THF

ߢ߽޽߹ࠅᏅߩ ߥ޿⚿ᨐߣߥߞߚ㧚৻ᣇ㧘ࡋࠠࠨࡦṁᇦߢߪ㧘෻

ᔕᕈߥࠄ߮ߦㆬᛯᕈߣ߽⧯ᐓૐ޿⚿ᨐߣߥߞߚ㧚

Table 6. The effect of solvent.^a)

Entry Solvent Yield (%)^b) E.e.^c)

(% ee) Config.^d)

1 CH2Cl2 86 88 R

2 Toluene 79 85 R

3 Hexane 71 72 R

4 THF 77 88 R

a) Reaction Conditions: benzaldehyde : Ligand (6) : Ti(O-i-Pr)4 : Et2Zn = 1.0 : 0.2 : 1.4 : 3.0 (molar ratio), r.t., 24 h. b) Determined by GLC. c) DAICEL CHIRALCEL OB, Hexane / i-PrOH = 90 / 10, 0.5 mL/min, uv 254 nm㧚d) See experimental section㧚

D㈩૏ሶߩ㊂ߩᓇ㗀 (Table 7)

࠴࠲ࡦߩߺߢߪ෼₸

39%

ߢ޽ࠅ㧘㈩૏ሶࠍ

5

mol%ട߃ߚߣ߈ߦࠛ࠽ࡦ࠴ࠝㆬᛯᕈߪ 94%

ee ߣ

㜞ߊ㧘

40 mol%

ߢߪࠛ࠽ࡦ࠴ࠝㆬᛯᕈߪ

83%

eeߣ

ૐਅߒ㧘෼₸߽

66%ߣૐਅߒߚ㧚

Table 7. The effect of ligand to Ti(O-i-Pr)4.^a) Entry Ligand 6

( mol%)^b) Yield

(%)^c) E.e. (% ee)^d) Config.^e)

1 0 39 racemic 㧙

2 2 100 89 R

3 5 98 94 R

4 10 80 87 R

5 20 86 88 R

6 40 66 83 R

a) Raction Conditions: benzaldehyde : Ti(O-ⁱPr)4 : Et2Zn = 1.0 : 1.4 : 3 (molar ratio), r.t., 24 h. b) Based on Ti(O-i-Pr)4. c) Determined by GLC. d) DAICEL CHIRALCEL OB, Hexane / i-PrOH = 90 / 10, 0.5 mL / min, uv 254 nm. e) See experimental section.

E෻ᔕ᷷ᐲ㧘ࠫࠛ࠴࡞੝㋦㧘࠴࠲ࡦ㊂ߩᓇ㗀

⚿ᨐࠍ

Table 8

ߦ␜ߒߚ㧚৻⥸ߦਇᢧ⸅ᇦ෻ᔕ

ߪ㧘෻ᔕ᷷ᐲ߇ૐਅߔࠆߦᓥ޿ࠛ࠽ࡦ࠴ࠝㆬᛯᕈ ߇㜞ߊߥࠆ߇㧘ᧄ෻ᔕߢߪቶ᷷ߢ෻ᔕࠍⴕߞߚᤨ

߇෼₸

98%

㧘ࠛ࠽ࡦ࠴ࠝㆊ೾₸

94% ee

ߣᦨ߽⦟

޿⚿ᨐ߇ᓧࠄࠇߚ (Entry 3)㧚

࠴࠲ࡦߩ㊂ࠃࠅዋߥ޿ࠫࠛ࠴࡞੝㋦ߩ㊂ߢ෻ᔕ ࠍⴕߞߚߣߎࠈ㧘෼₸㧘ࠛ࠽ࡦ࠴ࠝㆊ೾₸ߣ߽ߦ ᄢ߈ߥᄌൻߪߥ߆ߞߚ㧚

Entry 5

ߢߪ

5

ᒰ㊂ߣㆊ೾

ߦട߃ߚ߇෻ᔕ߳ߩᓇ㗀ߪߥ߆ߞߚ㧚߹ߚ㧘࠴࠲

ࡦ ߩ ㊂ ߇ ዋ ߥ ߊ ߥ ࠆ ߣ ┙ ૕ ㆬ ᛯ ᕈ ߪ ૐ ਅ ߒ ߚ

(Entries 3, and 6-9)㧚

Table 8. Addition of diethylzinc to benzaldehyde.^a)

Entry Et₂Zn^b) (equiv.)

Ti(O-i-Pr)₄^b) (equiv.)

Temp.

(°C)

1-Phenyl-1-propanol Yield ^c)

(%)

E.e. ^d) (Config.)

1 3.0 1.4 -78 - -

2 3.0 1.4 0 96 89(R)

3 3.0 1.4 r.t. 98 94(R)

4 1.2 1.4 r.t. 99 91(R)

5 5.0 1.4 r.t. 99 94(R)

6 3.0 0.075 r.t. 16 75(R) 7 3.0 0.313 r.t. 99 66(R) 8 3.0 0.625 r.t. 99 85(R)

9 3.0 1.25 r.t. 98 93(R)

a) Reaction Conditions: benzaldehyde : ligand 6 = 1.0 : 0.05, r.t., 6 h.

b) Based on aldehyde. c) Determined by GLC. d) DAICEL CHIRAL- CEL OB, Hexane / i-PrOH = 90 / 10, 0.5 mL/min, uv 254 nm.

⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃ߩᬌ⸛

⚿ᨐࠍ

Table 9

ߦ␜ߔ㧚ࡔ࠻ࠠࠪၮࠍ᦭ߔࠆࠕ

࠾ࠬࠕ࡞࠺ࡅ࠼ߢߪࡄ࡜㧘ࡔ࠲㧘ࠝ࡞࠻૏ߩ㗅ߦ

෼₸㧘ࠛ࠽ࡦ࠴ࠝㆬᛯᕈߣ߽ߦᷫዋߒߚ㧚ࠢࡠࡠ ࡌࡦ࠭ࠕ࡞࠺ࡅ࠼ߢ߽ห᭽ߩ⚿ᨐߣߥߞߚ㧚⟎឵

ၮ߇ࠕ࡞࠺ࡅ࠼ၮߦㄭߊߥࠆߦᓥ޿┙૕⊛ߥᓇ㗀 ߦࠃࠅਛᔃ㊄ዻߦኻߒߡࠞ࡞ࡏ࠾࡞ၮ߇㈩૏ߒߦ ߊߊ㧘෻ᔕᕈߣ┙૕ㆬᛯᕈ߇ૐਅߒߚߩߢߪߥ޿

߆ߣ⠨߃ࠄࠇࠆ㧚

1-

࠽ࡈ࠻ࠕ࡞࠺ࡅ࠼㧘

2-

࠽ࡈ࠻

ࠕ࡞࠺ࡅ࠼ߩࠃ߁ߦ㕖Ᏹߦ፾㜞޿ࠕ࡞࠺ࡅ࠼ߦߟ

޿ߡ߽ᬌ⸛ߒߚߣߎࠈ㧘ࠛ࠽ࡦ࠴ࠝㆬᛯᕈߪ

95%

ee ߣᦨ߽⦟޿⚿ᨐߣߥߞߚ㧚᩵⊹ࠕ࡞࠺ࡅ࠼ߢߪ㧘

෻ᔕᕈߪ㜞޿߽ߩߩ┙૕ㆬᛯᕈߪૐਅߒߚ㧚

123

Table 9. Asymmetric addition of diethylzinc to various aldehydes.^a)

Entry Aldehydes (RCHO) R =

Yield (%)^b)

E.e.^c)

(% ee) Config.^d)

1 C6H5 98 94 R

2 4-CH3C6H4 89 88 R

3 3-CH3OC6H4 74 91 R

4 2-CH3C6H4 72 82 R

5 4-ClC6H4 77 92 R

6 2-ClC6H4 78 77 R

7 2-naphthyl 93 95 R

8 1-naphthyl 84 95 R

9 C6H5CH=CH 85 69 R

a) Reaction conditions: aldehyde : ligand (6) : Ti(O-i-Pr)4 : Et2Zn = 1.0 : 0.05 : 1.4 : 3.0 (molar ratio), r.t., 6 h. b) Determined by GLC. c) DAICEL CHIRALCEL OB, hexane / i-PrOH = 90 / 10, 0.5 mL/min, uv 254 nm. d) See experimental section.

෻ᔕᯏ᭴ߩ⠨ኤ

0ࡈ࠲ࡠࠗ࡞1࠻࡝࠴࡞ࠠ࠻ࠨࡦࠍ㈩

૏ሶߣߔࠆ⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩࠫࠛ࠴࡞੝㋦

ߦࠃࠆਇᢧઃട෻ᔕߩ෻ᔕᯏ᭴

Zn

Et Et X Zn Et

10 11

Y

Scheme 5. Structure of zinc reagents.

⋥✢ಽሶߢ޽ࠆࠫࠛ࠴࡞੝㋦ (10) ߪ

sp

ᷙᚑ゠

㆏ࠍᜬߜ㧘὇⚛੝㋦⚿วߩಽᭂ߇ዊߐߊ㧘ࠕ࡞࠺

ࡅ࠼㘃ߦኻߒߡਇᵴᕈߢ޽ࠆ㧚ߒ߆ߒ㧘ㆡᒰߥൻ ว‛ߩ㈩૏ߦࠃߞߡᦛ✢᭴ㅧ 11 ࠍߣࠆߣ੝㋦ේ

ሶߦ߅ߌࠆಽሶ゠㆏ߩ

p

ᕈ߇㜞߹ߞߡ㔚ሶࠍᒁ߈ ነߖߦߊߊߥࠅ㧘߹ߚ὇⚛㧙੝㋦⚿ว߇ࠃࠅᄢ߈ ߊಽᭂߔࠆߚ߼ߦࠕ࡞࠺ࡅ࠼㘃ߦኻߒߡࠕ࡞ࠠ࡞

ၮߩォ⒖߇น⢻ߣߥࠆ

(Scheme 5)

㧚

O N

OH O

O O

Et₂Zn

O N

O O

O O

Zn Et

OTr OTr

2c 12

C₂H₆

Scheme 6. Plausible active intermediate.

శቇᵴᕈ ȕ-ࠕࡒࡁࠕ࡞ࠦ࡯࡞ߩሽ࿷ਅࠫࠛ࠴࡞

੝㋦ߩࡌࡦ࠭ࠕ࡞࠺ࡅ࠼߳ߩઃട෻ᔕߦ߅޿ߡ㊁

ଐࠄ ^24,25) ߦࠃߞߡឭ᩺ߐࠇߚ෻ᔕᯏ᭴ࠍෳ⠨ߦ㧘

2c ࠍ↪޿ߚᤨߩᵴᕈ⒳ࠍ⠨ኤߒߚ

(Scheme 6)

㧚 ㊁ଐࠄߩ෻ᔕߦ߅޿ߡߪࠕࡒࡁࠕ࡞ࠦ࡯࡞ࠍ㈩

૏ሶߣߒߡ↪޿ߡ޿ࠆߚ߼㧘ࠕࡒࡁၮߣ᳓㉄ၮ߇

ࠫࠛ࠴࡞੝㋦ߣ෻ᔕߒߡ੝㋦㍲૕ࠍ↢ᚑߔࠆߣឭ

᩺ߒߡ޿ࠆ㧚ᧄ෻ᔕߢߪ㧘ࠕࡒࡁၮߪࡈ࠲ࡠࠗ࡞

ൻߐࠇߡ޿ࠆߎߣ߆ࠄ㧘2c ߩ⓸⚛ේሶߪ㈩૏ߒ㔍 ߊ㧘ࠞ࡞ࡏ࠾࡞㉄⚛߇㈩૏ߒߡ 12 ߩ੝㋦㍲૕ࠍ

↢ᚑߔࠆߣᕁࠊࠇࠆ㧚ߎࠇߪࡌࡦࠫ࡞ൻࠠ࠻ࠨࡦ 㘃 1d ߿ 1e ࠃࠅࡈ࠲࡞ࠗࡒ࠼ൻߒߚ 2c ߿ 2e㧘

߹ߚ

3

૏ߩ᳓㉄ၮ߇ሽ࿷ߔࠆ 2c ߦ߅޿ߡ㜞޿శ ቇ෼₸߇ᓧࠄࠇߚߎߣ߆ࠄᡰᜬߐࠇࠆ㧚

㧰ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕࠴࠲ࡦ㍲૕ࠍ

↪޿ߚࠫࠛ࠴࡞੝㋦ߦࠃࠆ⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳

ߩਇᢧઃട෻ᔕߦ߅ߌࠆ෻ᔕᯏ᭴

੍ᗐߐࠇࠆ෻ᔕᯏ᭴ࠍ

Scheme 7

ߦ␜ߒߚ㧚߹

ߕ㧘㈩૏ሶߣ࠴࠲ࡦ

(IV)

࠹࠻࡜ࠗ࠰ࡊࡠࡐࠠࠪ࠼

߇෻ᔕߒߚᓟ㧘ࠫࠛ࠴࡞੝㋦ߣ⚿วߒߡ㧘࠴࠲ࡦ 㧙੝㋦㍲૕ 13 ߇ᒻᚑߐࠇࠆ㧚ࡌࡦ࠭ࠕ࡞࠺ࡅ࠼

ߩࠞ࡞ࡏ࠾࡞㉄⚛߇࠴࠲ࡦߦ㈩૏ߒ㧘ࠛ࠴࡞ၮ߇

ࠞ࡞ࡏ࠾࡞὇⚛ࠍ᡹᠄ߒߡ࠴࠲ࡦ㍲૕ 15 ߇ᒻᚑ ߒ㧘ࠕࠠ࡜࡞ߥ࠴࠲ࡦ㧙੝㋦㍲૕ 14 ߦࠃࠅ 13 ߇ౣ↢ߔࠆߣ⠨߃ࠄࠇࠆ㧚

࠴࠲ࡦߩ㊂߇Ⴧടߔࠆߦߟࠇߡ෻ᔕㅦᐲ㧘ࠛ࠽

ࡦ࠴ࠝࡑ࡯ㆊ೾₸߽Ⴧടߒߚ㧚ߎߩߎߣߪ㧘࠴࠲

ࡦ㍲૕ 14 ߩ㊂߇Ⴧ߃ࠆߎߣߢ15 ߣߩ෻ᔕ߇ട ㅦߐࠇߡᵴᕈ⒳ 13 ߇ߢ߈߿ߔߊߥࠆߣ⠨߃ࠄࠇ ࠆ㧚߹ߚ㧘࠴࠲ࡦ

(IV)

࠹࠻࡜ࠗ࠰ࡊࡠࡐࠠࠪ࠼ࠍ

㈩૏ሶࠃࠅ߽ㆊ೾ߦട߃ߚ߶߁߇㧘⸅ᇦല₸߇㜞

߹ࠆℂ↱ߣߒߡ㧘ࠕ࡞࠺ࡅ࠼ߣ෻ᔕߒߡ↢ᚑߔࠆ

࠴࠲ࡦ㍲૕ 15 ߪࠫࠛ࠴࡞੝㋦޽ࠆ޿ߪ 14 ߦࠃ ߞߡ 13 ߦౣ↢ߐࠇࠆ(Scheme 7)㧚ߎߩᤨ㧘ࠫࠛ࠴

࡞੝㋦ࠃࠅ߽ 14 ߩᣇ߇㧘ㅦ߿߆ߦ 13 ࠍౣ↢ߔ ࠆߚ߼ߢߪߥ޿߆ߣ⠨߃ࠄࠇࠆ^26,27)㧚

キトサン，D-(+)-グルコサミン誘導体を配位子とする金属錯体存在下でのジエチル亜鉛の芳香族アルデヒド類への触媒的不斉付加反応

O NAc O O

OBn MeO O

i-Pr-O Ti O-i-Pr

O NAc O O

OBn MeO O

i-Pr-O Ti

Et Ph

O

Et Ph

Ti O

i-Pr i-Pr-O i-Pr-O

O [O-(Et)Zn-Ti(O-i-Pr)₄] H

14

O NHAc HO

O

OBn MeO O

Ti(O-i-Pr)4

2i-PrOH

O i-Pr

ZnEt₂

O NAc O O

OBn MeO O

i-Pr-O Ti O-i-Pr Et₂Zn

Et₂Zn

(i-PrO)EtZn 13

15

Scheme 7. Reaction mechanism.

✚᜝

એ਄㧘ᧄ⎇ⓥߢߪ㧘౉ᚻኈᤃߢ቟ଔߥࠠ࠻ࠨࡦ㧘

D

-(+)-

ࠣ࡞ࠦࠨࡒࡦ߆ࠄኈᤃߦวᚑߢ߈ࠆࠠ࠻ࠨࡦ

⺃ዉ૕㧘D

-(+)-ࠣ࡞ࠦࠨࡒࡦ⺃ዉ૕ࠍ㈩૏ሶߣߔࠆ

ࠫࠛ࠴࡞੝㋦ߩ⧐㚅ᣖࠕ࡞࠺ࡅ࠼㘃߳ߩ⸅ᇦ⊛ਇ ᢧઃട෻ᔕࠍᬌ⸛ߒ㧘㜞޿ࠛ࠽ࡦ࠴ࠝㆬᛯᕈߣ㜞

޿෼₸ߢ⋡⊛↢ᚑ‛߇ᓧࠄࠇࠆߎߣࠍ᣿ࠄ߆ߦߒ ߚ㧚ᄤὼ↱᧪‛⾰ߢ޽ࠆࠠ࠻ࠨࡦ⺃ዉ૕㧘D

-(+)-ࠣ

࡞ࠦࠨࡒࡦ⺃ዉ૕ࠍ㈩૏ሶߣߒߡ↪޿ࠆᚻᴺߩ㐿

⊒ߪ㧘቟ଔߢ◲නߦశቇᵴᕈ╙ੑ⚖ࠕ࡞ࠦ࡯࡞ࠍ ᓧࠆᣇᴺߣߒߡ㕖Ᏹߦ᦭ലߢ޽ࠆߣ⠨߃ࠄࠇࠆ㧚

ෳ⠨ᢥ₂

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(1990) ᛛႎၴ಴ 㧚 b) ࠠ࠴ࡦ, ࠠ࠻ࠨࡦታ㛎ࡑ࠾

ࡘࠕ࡞, ࠠ࠴ࡦ, ࠠ࠻ࠨࡦ⎇ⓥળ✬ (1990) ᛛႎၴ಴

 㧚c) ࠠ࠴ࡦ, ࠠ࠻ࠨࡦࡂࡦ࠼ࡉ࠶ࠢ, ࠠ࠴ࡦ, ࠠ

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キトサン，D-(+)-グルコサミン誘導体を配位子とする金属錯体存在下でのジエチル亜鉛の芳香族アルデヒド類への触媒的不斉付加反応